The Effect of Fexofenadine on Pruritus in a Mouse Model (HR-ADf) of Atopic Dermatitis

Akamatsu, Hirohiko; Makiura, Munehiko; Yamamoto, Naoki; Yagami, Akiko; Shimizu, Yoshinori; Matsunaga, K.

doi:10.1177/147323000603400506

Cited by 9 publications

(7 citation statements)

References 14 publications

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“…H1R antagonists, used in clinical practice such as olopatadine, 55,69,89 pyrilamine, 90 cetirizine 83 and fexofenadine, 91 were confirmed the usefulness to allergic dermatitis models in mice. However, an antagonism of H1R has only limited effects in skin inflammation.…”

Section: Effects Of the Co-administration Of H1r Antagonists And H4r mentioning

confidence: 84%

The Role of Histamine H1 and H4 Receptors in Atopic Dermatitis: From Basic Research to Clinical Study

Ohsawa

Hirasawa

2014

Allergology International

114

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Histamine plays important roles in inflammation and nervous irritability in allergic disorders, including atopic dermatitis (AD). It has been shown to regulate the expression of pruritic factors, such as nerve growth factor and semaphorin 3A, in skin keratinocytes via histamine H1 receptor (H1R). Furthermore, H1R antagonist reduced the level of IL-31, a cytokine involving the skin barrier and pruritus, in chronic dermatitis lesions in NC/Nga mice and patients with AD. Histamine plays roles in the induction of allergic inflammation by activating eosinophils, mast cells, basophils, and Th2 cells via histamine H4 receptor (H4R). H4R, in addition to H1R, is expressed on sensory neurons, and a decrease in scratching behaviors was observed in H4R-deficient mice and mice treated with a H4R antagonist. We found that the combined administration of H1R and H4R antagonists inhibited the itch response and chronic allergic inflammation, and had a pharmacological effect similar to that of prednisolone. Although the oral administration of H1R antagonists is widely used to treat AD, it is not very effective. In contrast, JNJ39758979, a novel H4R antagonist, had marked effects against pruritus in Japanese patients with AD in a phase II clinical trial. Next generation antihistaminic agents possessing H1R and H4R antagonistic actions may be a potent therapeutic drug for AD.

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Section: Effects Of the Co-administration Of H1r Antagonists And H4r mentioning

confidence: 84%

The Role of Histamine H1 and H4 Receptors in Atopic Dermatitis: From Basic Research to Clinical Study

Ohsawa

Hirasawa

2014

Allergology International

114

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“…Mg 2+ deficiency induces apoptosis in isolated hepatocytes (Martin et al , 2003) and increases incidence of stroke, hypertension, eclampsia, and atherosclerosis (Saris et al , 2000). Interestingly, magnesium deficiency has been widely used in rodents to experimentally model atopic dermatitis associated with a robust scratching behavior (Akamatsu et al , 2006; Biro et al , 2005; Neckermann et al , 2000). However, the mechanisms underlying the hypomagnesemia-mediated skin disorders are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Tonic Inhibition of TRPV3 by Mg2+ in Mouse Epidermal Keratinocytes

Luo

Stewart

Berdeaux

et al. 2012

Journal of Investigative Dermatology

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The transient receptor potential vanilloid 3 channel (TRPV3) is abundantly expressed in epidermal keratinocytes and plays important roles in sensory biology and skin health. Mg2+ deficiency causes skin disorders under certain pathological conditions such as type 2 diabetes mellitus. In this study, we investigated the effect of Mg2+ on TRPV3 in primary epidermal keratinocytes. Extracellular Mg2+ ([Mg2+]o) inhibited TRPV3-mediated membrane current and calcium influx. TRPV3 activation induced a calcium signaling pathway culminating in activation of the cAMP response element binding (CREB). TRPV3 inhibition by [Mg2+]o, the TRPV3 blocker ruthenium red or TRPV3 siRNA suppressed this response. In TRPV3-expressing Chinese hamster ovary (CHO) cells, both extracellular and intracellular Mg2+ inhibited TRPV3 single-channel conductance but not open probability. Neutralization of an aspartic acid residue (D641) in the extracellular pore loop or two acidic residues (E679, E682) in the inner pore region significantly attenuated the inhibitory effect of extracellular or intracellular Mg2+ on TRPV3-mediated signaling, respectively. Our findings suggest that epidermal TRPV3 is tonically inhibited by both extracellular and intracellular Mg2+, which act on both sides of the channel pore loop. Mg2+ deficiency may promote the function of TRPV3 and contribute to the pathogenesis of skin diseases.

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“…There was statistical significance between HR-AD-fed mice and wasabi dietfed mice. Akamatsu et al made AD-like model mice using a special diet including magnesium of 1,400 mg/ kg (23,25). In our study, magnesium in wasabi rhizome extract is low; it appeared that magnesium derived from wasabi was not a key substance involved in the improvement of the AD-like symptoms.…”

Section: Effects Of Wasabi Rhizome Extract On the Plasma Components Amentioning

confidence: 76%

“…The scratching behavior of the mice was analyzed and recognized at three time points: 28, 35 and 42 d after starting the special diet. Mice were videotaped for 30 min, and the frequency of scratching was counted retrospectively at sequential 5-min intervals ( 23 ). Scratching frequency was defined as scratching the neck with the hind limbs.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Wasabi Rhizome Extract on Atopic Dermatitis-Like Symptoms in HR-1 Hairless Mice

Nagai¹,

Okunishi²

2009

J Nutr Sci Vitaminol

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SummaryWe investigated the effect of wasabi rhizome extract on atopic dermatitis (AD) model mice. The wasabi extract was fed to the HR-1 hairless mice, which develop AD-like symptoms with a special diet (HR-AD diet). The extract was expected to reduce the symptoms induced. Wasabi rhizome-containing HR-AD diet (5% and 10%) reduced the scratching behavior, and the 10% wasabi rhizome HR-AD diet significantly reduced scratching behavior on days 28, 35 and 42. Plasma components (histamine, eotaxin, IgE and thymus and activation-regulated chemokine (TARC)) were decreased in the 10% wasabi rhizome HR-AD diet. In histopathological examinations (toluidine blue (T.B.), major basic protein (MBP), CD4, IL-4, IL-5, eotaxin, TARC and IgE), the wasabi rhizome-containing HR-AD diet (5% and 10%) significantly reduced the number of positive stained cells. These results suggested that the wasabi rhizome extract improved the AD-like symptoms of HR-1 hairless mice.

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The Effect of Fexofenadine on Pruritus in a Mouse Model (HR-ADf) of Atopic Dermatitis

Cited by 9 publications

References 14 publications

The Role of Histamine H1 and H4 Receptors in Atopic Dermatitis: From Basic Research to Clinical Study

The Role of Histamine H1 and H4 Receptors in Atopic Dermatitis: From Basic Research to Clinical Study

Tonic Inhibition of TRPV3 by Mg2+ in Mouse Epidermal Keratinocytes

The Effect of Wasabi Rhizome Extract on Atopic Dermatitis-Like Symptoms in HR-1 Hairless Mice

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